高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数

本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4～5.6%,血浓69.6～1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。     

Plasma levels of alpha beta peptides are altered in amnestic mild cognitive impairment but not in sporadic Alzheimer's disease

Plasma alpha beta levels have been examined in sporadic Alzheimer's disease yielding conflicting results; both no difference and an increase in plasma concentrations of alpha beta42 and alpha beta40 in sporadic cases of AD as compared to controls have been reported. Elevated plasma alpha beta42 levels may be detected several years before the onset of symptoms (in mild cognitive impairment stadium). Levels of alpha beta40 and alpha beta42 were measured in plasma from 54 patients with AD, 39 subjects with MCI and 35 controls using a commercially available ELISA. Mean plasma alpha beta42 levels were significantly higher in MCI as compared to both AD (P < 0.001) and control subjects (P < 0.001), while alpha beta40 did not differ between the groups. No correlations were observed between alpha beta levels and age, MMSE scores or gender. According to ROC curve analysis the maximum accuracy in discriminating MCI versus both controls and AD subjects has been achieved using a cut-off value of 3.8.     

The UTX gene escapes X inactivation in mice and humans

We recently have identified a ubiquitously transcribed mouse Y chromosome gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A peptide derived from the UTY protein confers H-Y antigenicity on male cells. Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2. Given that Uty is ubiquitously transcribed, we assayed for Utx expression from the inactive X chromosome (Xi) in mice and found that Utx escapes X chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the mouse X chromosome have been reported previously to escape inactivation. The human UTX gene was also found to be expressed from Xi. We discuss the significance of these data for our understanding of dosage compensation of X-Y homologous genes in humans and mice.      

Pathology and Immunocytochemistry of a Kuru Brain

We report here results of modern staining techniques including anti-prion protein (PrP) immunocytochemistry to a set of archival brain specimens of a 16 year-old male who died from kuru in 1967. Brain suspensions transmitted disease to chimpanzees and New World monkeys. The PrP gene is homozygous for valine at the polymorphic codon 129. Histology shows neuronal loss, spongiform change, and astrogliosis. Lesions are maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, striatum, and thalamus, and are accentuated in middle and deep cerebral cortical layers. PrP accumulates as diffuse synaptic type deposits and mostly unicentric plaques. PrP deposition is maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, basal ganglia, and cerebellar cortex. Plaques are prominent in the striatum, thalamus, and granular layer of cerebellar cortex. Meticulous examination reveals only rare "florid" plaques with surrounding vacuolation.
We conclude that 1) pathology including immunomorphology of PrP deposition in this kuru brain is within the lesion spectrum of Creutzfeldt-Jakob disease although plaques are unusually prominent and widespread; 2) kuru does not share the neuropathological hallmarks of the new Creutzfeldt-Jakob disease variant recently reported in the UK and France; 3) topographic prominence of PrP deposition parallels that of spongiform change and/or astrogliosis.     

L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns

L1 is a neural cell adhesion molecule mainly involved in axon guidance and neuronal migration during brain development. Mutations in the human L1 gene give rise to a complex clinical picture, with mental retardation, neurologic abnormalities and a variable degree of hydrocephalus. Recently, a transgenic mouse model with a targeted null mutation in the L1 gene was generated. These knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have performed further studies of these KO mice including magnetic resonance imaging of the brain, neuropathological analysis and behavioral testing. The ventricular system was shown to be abnormal with dilatation of the lateral ventricles and the 4th ventricle, and an altered shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the KO mice is hypoplastic. Their exploratory behavior is characterized by stereotype peripheral circling reminiscent of that of rodents with induced cerebellar lesions.      

Ultrastructural changes in the optic nerves of rodents with experimental Creutzfeldt-Jakob Disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS) or scrapie

This report describes the ultrastructural changes in the optic nerves of (1) hamsters infected with the Echigo-1 strain of Creutzfeldt-Jakob disease (CJD), (2) hamsters infected with the 263K or 22C-H strain of scrapie, and (3) mice infected with the Fujisaki strain of Gerstmann-Str?ussler-Scheinker disease (GSS). Vacuolation of myelinated fibres was present in the myelin sheaths, with splitting of myelin lamellae. These vacuoles contained typical secondary vacuoles and curled membrane fragments. Myelinated fibre vacuolation was also accompanied by an exuberant cellular reaction consisting of macrophages containing numerous mitochondria, abundant rough endoplasmic reticulum, and secondary lysosomes filled with digested myelin debris and other electron-dense material. Within macrophages, myelin fragments undergoing active digestion, lyre-like bodies and paracrystalline inclusions were frequently noted. Astrocytes and their processes were prominent; glial filaments and many mitochondria were readily detected. Proliferation of inner mesaxons was observed. Cross-sectional profiles of innumerable myelinated fibres contained membranous organelles continuous with the inner lamellae of the oligodendroglial cells. The proliferations of inner mesaxons formed whorls and loops, and intrusion of the membranous tongue of the inner mesaxon into the axoplasm was occasionally observed; dystrophic neurites were relatively numerous. In mice infected with the Fujisaki strain of GSS, fibres had undergone demyelination with stripping of the myelin lamellae, while others showed vesicular myelin degeneration.     

Brain histamine metabolism in transmissible spongiform encephalopathy (Scrapie)

Summary The histamine (Hi) content and the activity of L-histidine decarboxylase (HD) in brains of scrapie infected hamsters were measured. No significant changes in Hi levels in particular brain areas were found when compared to controls. Decreased activity of HD was found in hypothalamus (p<0.02). Increased activity of the enzyme was observed in rest of brain, which consisted mainly of thalamus and striatum (p<0.05).